CA2727103A1 - Naphtyridinones en tant qu'inhibiteurs d'aurora kinase - Google Patents

Naphtyridinones en tant qu'inhibiteurs d'aurora kinase Download PDF

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Publication number: CA2727103A1
Authority: CA; Canada
Prior art keywords: phenyl; benzamide; amino; naphthyridin; oxo
Prior art date: 2008-07-03
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA2727103A

Other languages

English (en)

Inventor

Yufang Xiao

Xiaoling Chen

Srinivasa R. Karra

Bayard R. Huck

Amanda E. Sutton

Andreas Goutopoulos

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck Patent GmbH

Original Assignee

Merck Patent GmbH

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2008-07-03

Filing date

2009-06-29

Publication date

2010-01-07

2009-06-29 Application filed by Merck Patent GmbH filed Critical Merck Patent GmbH

2010-01-07 Publication of CA2727103A1 publication Critical patent/CA2727103A1/fr

Status Abandoned legal-status Critical Current

Links

239000003719 aurora kinase inhibitor Substances 0.000 title description 4
-1 Naphthyridinone derivative compounds Chemical class 0.000 claims abstract description 213
150000001875 compounds Chemical class 0.000 claims abstract description 185
238000000034 method Methods 0.000 claims abstract description 103
206010028980 Neoplasm Diseases 0.000 claims abstract description 38
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
201000010099 disease Diseases 0.000 claims abstract description 24
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
208000023275 Autoimmune disease Diseases 0.000 claims abstract description 6
230000002062 proliferating effect Effects 0.000 claims abstract description 6
201000004681 Psoriasis Diseases 0.000 claims abstract description 5
208000035143 Bacterial infection Diseases 0.000 claims abstract description 3
208000036142 Viral infection Diseases 0.000 claims abstract description 3
208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 3
230000003612 virological effect Effects 0.000 claims abstract description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 100
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
125000000217 alkyl group Chemical group 0.000 claims description 65
239000000203 mixture Substances 0.000 claims description 65
125000000623 heterocyclic group Chemical group 0.000 claims description 43
125000003118 aryl group Chemical group 0.000 claims description 40
150000003839 salts Chemical class 0.000 claims description 40
229910052717 sulfur Inorganic materials 0.000 claims description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
125000001072 heteroaryl group Chemical group 0.000 claims description 30
125000005843 halogen group Chemical group 0.000 claims description 29
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 28
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 25
150000002148 esters Chemical class 0.000 claims description 25
125000004404 heteroalkyl group Chemical group 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
125000004103 aminoalkyl group Chemical group 0.000 claims description 24
125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 24
125000005842 heteroatom Chemical group 0.000 claims description 23
229910052760 oxygen Inorganic materials 0.000 claims description 23
239000000651 prodrug Substances 0.000 claims description 22
229940002612 prodrug Drugs 0.000 claims description 22
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 20
239000000243 solution Substances 0.000 claims description 20
125000003418 alkyl amino alkoxy group Chemical group 0.000 claims description 19
239000012453 solvate Substances 0.000 claims description 19
239000003814 drug Substances 0.000 claims description 16
229920006395 saturated elastomer Polymers 0.000 claims description 16
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
239000004480 active ingredient Substances 0.000 claims description 13
125000003282 alkyl amino group Chemical group 0.000 claims description 13
201000011510 cancer Diseases 0.000 claims description 13
150000001733 carboxylic acid esters Chemical class 0.000 claims description 13
239000011593 sulfur Substances 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 12
125000005128 aryl amino alkyl group Chemical group 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
125000004663 dialkyl amino group Chemical group 0.000 claims description 12
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125000005241 heteroarylamino group Chemical group 0.000 claims description 12
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
238000006467 substitution reaction Methods 0.000 claims description 12
FGPWYCKELFZGGE-UHFFFAOYSA-N 2-cyanato-2-oxoacetic acid Chemical compound OC(=O)C(=O)OC#N FGPWYCKELFZGGE-UHFFFAOYSA-N 0.000 claims description 11
125000004212 difluorophenyl group Chemical group 0.000 claims description 11
239000003085 diluting agent Substances 0.000 claims description 11
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 11
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150000001602 bicycloalkyls Chemical group 0.000 claims description 10
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 9
125000002252 acyl group Chemical group 0.000 claims description 9
125000004093 cyano group Chemical group *C#N 0.000 claims description 9
125000001188 haloalkyl group Chemical group 0.000 claims description 9
239000000546 pharmaceutical excipient Substances 0.000 claims description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 9
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 claims description 8
229910052757 nitrogen Inorganic materials 0.000 claims description 8
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 claims description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
125000002619 bicyclic group Chemical group 0.000 claims description 7
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208000035475 disorder Diseases 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
206010016654 Fibrosis Diseases 0.000 claims description 6
241000124008 Mammalia Species 0.000 claims description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
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HDLIWEMWMDOCHM-UHFFFAOYSA-N n-(4-chloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=CC(Cl)=CC=N1 HDLIWEMWMDOCHM-UHFFFAOYSA-N 0.000 claims description 5
239000000843 powder Substances 0.000 claims description 5
125000003944 tolyl group Chemical group 0.000 claims description 5
LTHRVXKIFSUUPQ-UHFFFAOYSA-N (2-amino-4-chloropyridin-3-yl)-phenylmethanone Chemical compound NC1=NC=CC(Cl)=C1C(=O)C1=CC=CC=C1 LTHRVXKIFSUUPQ-UHFFFAOYSA-N 0.000 claims description 4
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 4
206010052779 Transplant rejections Diseases 0.000 claims description 4
125000000068 chlorophenyl group Chemical group 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
239000008187 granular material Substances 0.000 claims description 4
MILJSIRQQVFCQK-UHFFFAOYSA-N n-(3-benzoyl-4-chloropyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=NC=CC(Cl)=C1C(=O)C1=CC=CC=C1 MILJSIRQQVFCQK-UHFFFAOYSA-N 0.000 claims description 4
BKDOLJNIDBPTJO-UHFFFAOYSA-N n-(4-aminophenyl)-2-(trifluoromethyl)benzamide Chemical compound C1=CC(N)=CC=C1NC(=O)C1=CC=CC=C1C(F)(F)F BKDOLJNIDBPTJO-UHFFFAOYSA-N 0.000 claims description 4
QYAKZKZDJPNJNR-UHFFFAOYSA-N n-(4-aminophenyl)-4-fluoro-2-(trifluoromethyl)benzamide Chemical compound C1=CC(N)=CC=C1NC(=O)C1=CC=C(F)C=C1C(F)(F)F QYAKZKZDJPNJNR-UHFFFAOYSA-N 0.000 claims description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
YFCRUCRIKVVGHI-UHFFFAOYSA-N 2-fluoro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound FC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 YFCRUCRIKVVGHI-UHFFFAOYSA-N 0.000 claims description 3
QQDOIMODMZLXTE-UHFFFAOYSA-N 3,4-difluoro-n-[4-[(6-nitro-7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C1=CN=C2NC(=O)C([N+](=O)[O-])=CC2=C1NC(C=C1)=CC=C1NC(=O)C1=CC=C(F)C(F)=C1 QQDOIMODMZLXTE-UHFFFAOYSA-N 0.000 claims description 3
206010018364 Glomerulonephritis Diseases 0.000 claims description 3
208000007536 Thrombosis Diseases 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
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208000019425 cirrhosis of liver Diseases 0.000 claims description 3
125000002474 dimethylaminoethoxy group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])O* 0.000 claims description 3
IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 claims description 3
230000004761 fibrosis Effects 0.000 claims description 3
YFJAIURZMRJPDB-UHFFFAOYSA-N n,n-dimethylpiperidin-4-amine Chemical compound CN(C)C1CCNCC1 YFJAIURZMRJPDB-UHFFFAOYSA-N 0.000 claims description 3
AVAWMINJNRAQFS-UHFFFAOYSA-N n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)C1CCNC1 AVAWMINJNRAQFS-UHFFFAOYSA-N 0.000 claims description 3
NHWHRFKTYLZJMO-UHFFFAOYSA-N n-(4-chloro-3-formylpyridin-2-yl)-2,2-dimethylpropanamide Chemical compound CC(C)(C)C(=O)NC1=NC=CC(Cl)=C1C=O NHWHRFKTYLZJMO-UHFFFAOYSA-N 0.000 claims description 3
XILBDNKHKZGJRZ-UHFFFAOYSA-N n-[2-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C=1C=CC=C(NC=2C=3C=CC(=O)NC=3N=CC=2)C=1NC(=O)C1=CC=CC=C1 XILBDNKHKZGJRZ-UHFFFAOYSA-N 0.000 claims description 3
QPNGGIZOZGOUFU-UHFFFAOYSA-N n-[4-[(7-chloro-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C=1C=NC2=NC(Cl)=CC=C2C=1NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 QPNGGIZOZGOUFU-UHFFFAOYSA-N 0.000 claims description 3
UHDNKQAXIVENRN-UHFFFAOYSA-N n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]-3,5-bis(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C(=O)NC=2C=CC(NC=3C=4C=CC(=O)NC=4N=CC=3)=CC=2)=C1 UHDNKQAXIVENRN-UHFFFAOYSA-N 0.000 claims description 3
CIIIYKOWERKQMN-UHFFFAOYSA-N n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]cyclohexanecarboxamide Chemical compound C=1C=C(NC=2C=3C=CC(=O)NC=3N=CC=2)C=CC=1NC(=O)C1CCCCC1 CIIIYKOWERKQMN-UHFFFAOYSA-N 0.000 claims description 3
HJHSUKDAIHEBBI-UHFFFAOYSA-N n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]pyrimidin-2-yl]benzamide Chemical compound N=1C=CC(NC=2C=3C=CC(=O)NC=3N=CC=2)=NC=1NC(=O)C1=CC=CC=C1 HJHSUKDAIHEBBI-UHFFFAOYSA-N 0.000 claims description 3
SVOKGUUJEXVDDV-UHFFFAOYSA-N n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)oxy]phenyl]benzamide Chemical compound C=1C=C(OC=2C=3C=CC(=O)NC=3N=CC=2)C=CC=1NC(=O)C1=CC=CC=C1 SVOKGUUJEXVDDV-UHFFFAOYSA-N 0.000 claims description 3
238000010992 reflux Methods 0.000 claims description 3
SJTJUWNIASJADU-UHFFFAOYSA-N tert-butyl 3-[4-chloro-2-(2,2-dimethylpropanoylamino)pyridin-3-yl]-3-hydroxypropanoate Chemical compound CC(C)(C)OC(=O)CC(O)C1=C(Cl)C=CN=C1NC(=O)C(C)(C)C SJTJUWNIASJADU-UHFFFAOYSA-N 0.000 claims description 3
YIFMENSEKOZKLN-UHFFFAOYSA-N 2,4-dichloro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound ClC1=CC(Cl)=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 YIFMENSEKOZKLN-UHFFFAOYSA-N 0.000 claims description 2
PKVOAZRSQHYLJD-UHFFFAOYSA-N 2,6-dichloro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound ClC1=CC=CC(Cl)=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 PKVOAZRSQHYLJD-UHFFFAOYSA-N 0.000 claims description 2
MEBLRIHZCVSNDZ-UHFFFAOYSA-N 2-(5-chloro-2-oxo-1h-1,8-naphthyridin-3-yl)acetic acid Chemical compound C1=CN=C2NC(=O)C(CC(=O)O)=CC2=C1Cl MEBLRIHZCVSNDZ-UHFFFAOYSA-N 0.000 claims description 2
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CXFPLAWBJLPBHA-UHFFFAOYSA-N 2-fluoro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]-4-(trifluoromethyl)benzamide Chemical compound FC1=CC(C(F)(F)F)=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 CXFPLAWBJLPBHA-UHFFFAOYSA-N 0.000 claims description 2
QKPYHSFZCMMVCV-UHFFFAOYSA-N 2-methoxy-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound COC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 QKPYHSFZCMMVCV-UHFFFAOYSA-N 0.000 claims description 2
RANQGSFJVSODKY-UHFFFAOYSA-N 2-methyl-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound CC1=CC=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 RANQGSFJVSODKY-UHFFFAOYSA-N 0.000 claims description 2
YSQGXXPINGXUSH-UHFFFAOYSA-N 3,4-dichloro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C1=C(Cl)C(Cl)=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 YSQGXXPINGXUSH-UHFFFAOYSA-N 0.000 claims description 2
UQHVUJGHRHOTDN-UHFFFAOYSA-N 3-fluoro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]-5-(trifluoromethyl)benzamide Chemical compound FC(F)(F)C1=CC(F)=CC(C(=O)NC=2C=CC(NC=3C=4C=CC(=O)NC=4N=CC=3)=CC=2)=C1 UQHVUJGHRHOTDN-UHFFFAOYSA-N 0.000 claims description 2
ALKSRRHOYIUUDG-UHFFFAOYSA-N 3-fluoro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound FC1=CC=CC(C(=O)NC=2C=CC(NC=3C=4C=CC(=O)NC=4N=CC=3)=CC=2)=C1 ALKSRRHOYIUUDG-UHFFFAOYSA-N 0.000 claims description 2
FMCHIONISPNEKG-UHFFFAOYSA-N 3-methyl-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound CC1=CC=CC(C(=O)NC=2C=CC(NC=3C=4C=CC(=O)NC=4N=CC=3)=CC=2)=C1 FMCHIONISPNEKG-UHFFFAOYSA-N 0.000 claims description 2
DAFOZSWKZSQPAM-UHFFFAOYSA-N 4,4-dihydroxybutanamide Chemical compound NC(=O)CCC(O)O DAFOZSWKZSQPAM-UHFFFAOYSA-N 0.000 claims description 2
WLYCEQDZYFAXOP-UHFFFAOYSA-N 4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]-n-phenylbenzamide Chemical compound C=1C=C(NC=2C=3C=CC(=O)NC=3N=CC=2)C=CC=1C(=O)NC1=CC=CC=C1 WLYCEQDZYFAXOP-UHFFFAOYSA-N 0.000 claims description 2
YPZZAAVUFKGCCK-UHFFFAOYSA-N 4-chloro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C1=CC(Cl)=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 YPZZAAVUFKGCCK-UHFFFAOYSA-N 0.000 claims description 2
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DUAAMDIJTOMESE-UHFFFAOYSA-N 4-fluoro-n-[4-[(6-nitro-7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]-2-(trifluoromethyl)benzamide Chemical compound C1=CN=C2NC(=O)C([N+](=O)[O-])=CC2=C1NC(C=C1)=CC=C1NC(=O)C1=CC=C(F)C=C1C(F)(F)F DUAAMDIJTOMESE-UHFFFAOYSA-N 0.000 claims description 2
XJYMHYVHNAMNAA-UHFFFAOYSA-N 4-fluoro-n-[4-[(7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C1=CC(F)=CC=C1C(=O)NC(C=C1)=CC=C1NC1=CC=NC2=C1C=CC(=O)N2 XJYMHYVHNAMNAA-UHFFFAOYSA-N 0.000 claims description 2
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GAHZMIFNGKXVSI-UHFFFAOYSA-N n',n'-dimethylpropanehydrazide Chemical group CCC(=O)NN(C)C GAHZMIFNGKXVSI-UHFFFAOYSA-N 0.000 claims description 2
JFHQBECHISXXKM-UHFFFAOYSA-N n-(4-aminophenyl)-2,4-dichlorobenzamide Chemical compound C1=CC(N)=CC=C1NC(=O)C1=CC=C(Cl)C=C1Cl JFHQBECHISXXKM-UHFFFAOYSA-N 0.000 claims description 2
BDJNVGBJARITCF-UHFFFAOYSA-N n-(4-aminophenyl)-2,4-difluorobenzamide Chemical compound C1=CC(N)=CC=C1NC(=O)C1=CC=C(F)C=C1F BDJNVGBJARITCF-UHFFFAOYSA-N 0.000 claims description 2
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CVPWYDXAVJCNAG-UHFFFAOYSA-N n-(4-hydroxyphenyl)benzamide Chemical compound C1=CC(O)=CC=C1NC(=O)C1=CC=CC=C1 CVPWYDXAVJCNAG-UHFFFAOYSA-N 0.000 description 1
RAGBTXOBAXRPTI-UHFFFAOYSA-N n-[4-[(5-hydroxy-7-oxo-8h-1,8-naphthyridin-4-yl)amino]phenyl]benzamide Chemical compound C=12C(O)=CC(=O)NC2=NC=CC=1NC(C=C1)=CC=C1NC(=O)C1=CC=CC=C1 RAGBTXOBAXRPTI-UHFFFAOYSA-N 0.000 description 1
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XNLBCXGRQWUJLU-UHFFFAOYSA-N naphthalene-2-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CC=C21 XNLBCXGRQWUJLU-UHFFFAOYSA-N 0.000 description 1
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238000012858 packaging process Methods 0.000 description 1
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
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125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
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OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical class OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
230000000865 phosphorylative effect Effects 0.000 description 1
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230000004962 physiological condition Effects 0.000 description 1
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239000011591 potassium Substances 0.000 description 1
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230000001737 promoting effect Effects 0.000 description 1
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125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
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230000001105 regulatory effect Effects 0.000 description 1
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125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
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239000010703 silicon Substances 0.000 description 1
230000004747 sister chromatid biorientation Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
GYBMSOFSBPZKCX-UHFFFAOYSA-N sodium;ethanol;ethanolate Chemical compound [Na+].CCO.CC[O-] GYBMSOFSBPZKCX-UHFFFAOYSA-N 0.000 description 1
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IXXMVXXFAJGOQO-UHFFFAOYSA-N tert-butyl 2-hydroxypropanoate Chemical compound CC(O)C(=O)OC(C)(C)C IXXMVXXFAJGOQO-UHFFFAOYSA-N 0.000 description 1
WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 1
BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P17/06—Antipsoriatics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Immunology (AREA)
Physical Education & Sports Medicine (AREA)
Communicable Diseases (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Oncology (AREA)
Vascular Medicine (AREA)
Transplantation (AREA)
Ophthalmology & Optometry (AREA)
Virology (AREA)
Orthopedic Medicine & Surgery (AREA)
Dermatology (AREA)
Diabetes (AREA)
Rheumatology (AREA)
Hematology (AREA)
Biomedical Technology (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA2727103A 2008-07-03 2009-06-29 Naphtyridinones en tant qu'inhibiteurs d'aurora kinase Abandoned CA2727103A1 (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US13401808P	2008-07-03	2008-07-03
US61/134,018		2008-07-03
PCT/US2009/049035 WO2010002779A2 (fr)	2008-07-03	2009-06-29	Naphtyridininones en tant qu’inhibiteurs d’aurora kinase

Publications (1)

Publication Number	Publication Date
CA2727103A1 true CA2727103A1 (fr)	2010-01-07

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Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2727103A Abandoned CA2727103A1 (fr)	2008-07-03	2009-06-29	Naphtyridinones en tant qu'inhibiteurs d'aurora kinase

Country Status (13)

Country	Link
US (1)	US20110269758A1 (fr)
EP (1)	EP2291376A2 (fr)
JP (1)	JP2011526912A (fr)
KR (1)	KR20110025856A (fr)
CN (1)	CN102083831B (fr)
AU (1)	AU2009267161B2 (fr)
BR (1)	BRPI0914936A2 (fr)
CA (1)	CA2727103A1 (fr)
EA (1)	EA201100126A1 (fr)
IL (1)	IL210377A (fr)
MX (1)	MX2010013842A (fr)
WO (1)	WO2010002779A2 (fr)
ZA (1)	ZA201008878B (fr)

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JP5826261B2 (ja) *	2010-06-28	2015-12-02	メルクパテントゲゼルシャフトミットベシュレンクテルハフツングＭｅｒｃｋＰａｔｅｎｔＧｅｓｅｌｌｓｃｈａｆｔｍｉｔｂｅｓｃｈｒａｅｎｋｔｅｒＨａｆｔｕｎｇ	癌に対する使用のためのキナーゼ阻害剤としての２，４−ジアリール置換［１，８］ナフチリジン
CN102408426B (zh) *	2011-09-14	2013-07-10	湖南有色凯铂生物药业有限公司	取代的芳香脲类化合物及其作为抗癌药物的应用
KR20180086187A (ko)	2015-10-05	2018-07-30	더 트러스티이스 오브 콜롬비아 유니버시티 인 더 시티 오브 뉴욕	자가포식 유동의 활성체 및 포스포리파제 d 및 타우를 포함하는 단백질 응집물의 클리어런스 및 단백질질환의 치료
CA3158951A1 (fr) *	2016-08-15	2018-02-22	Purdue Research Foundation	Derives d'aminoisoquinoleine substitues en position 4
KR102055660B1 (ko) *	2018-03-07	2019-12-13	경상대학교산학협력단	나프타미도-페닐아잔디일 유도체, 이를 포함하는 우라닐 이온 검출용 조성물 및 이를 이용한 우라닐 이온 검출 방법
KR102747104B1 (ko) *	2019-02-18	2024-12-27	한국과학기술연구원	단백질 키나아제 저해 활성을 갖는 신규한 피리도[3,4-d]피리미딘-8-온 유도체 및 이를 포함하는 암의 예방, 개선 또는 치료용 약학 조성물
WO2022146022A1 (fr) *	2020-12-29	2022-07-07	주식회사 티씨노바이오사이언스	Nouveau dérivé de naphthyridinone ayant une activité inhibitrice contre l'ectonucléotide pyrophosphatase/phosphodiestérase et son utilisation
KR102720206B1 (ko) *	2020-12-29	2024-10-21	주식회사 티씨노바이오사이언스	엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 나프티리딘온 유도체 및 이들의 용도
CN116669726A (zh) *	2020-12-29	2023-08-29	谛希诺生物科技有限公司	对外核苷酸焦磷酸酶-磷酸二酯酶具有抑制活性的新颖的萘啶酮衍生物及其用途
KR20250128292A (ko)	2022-09-26	2025-08-27	엣지와이즈 테라퓨틱스, 인크.	1,4-디하이드로퀴나졸리논 화합물 및 이의 용도
CN121194963A (zh) *	2023-03-27	2025-12-23	艾知怀斯治疗学公司	喹啉酮酰胺类化合物及其用途
WO2024206345A1 (fr)	2023-03-27	2024-10-03	Edgewise Therapeutics, Inc.	Composés de quinazoline dione et leurs utilisations

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GB9127252D0 (en) *	1991-12-23	1992-02-19	Boots Co Plc	Therapeutic agents
AR004010A1 (es) *	1995-10-11	1998-09-30	Glaxo Group Ltd	Compuestos heterociclicos
KR100567649B1 (ko) *	1996-09-25	2006-04-05	아스트라제네카 유케이 리미티드	혈관 내피 성장 인자와 같은 성장 인자의 효과를 억제하는 퀴놀린 유도체
GB9906566D0 (en) *	1999-03-23	1999-05-19	Zeneca Ltd	Chemical compounds
US7709479B1 (en) *	1999-09-21	2010-05-04	Astrazeneca	Quinazoline derivatives and their use as pharmaceuticals
EP1317450B1 (fr) *	2000-09-15	2006-11-22	Vertex Pharmaceuticals Incorporated	Composes de pyrazole utiles comme inhibiteurs de proteine kinase
DE60137273D1 (de) *	2000-10-20	2009-02-12	Eisai R&D Man Co Ltd	Verfahren zur Herstellung von 4-Phenoxy chinolin Derivaten
ES2290529T3 (es) *	2002-12-24	2008-02-16	Astrazeneca Ab	Derivados de fosfonooxiquinazolina y su uso farmaceutico.
PL378111A1 (pl) *	2003-02-14	2006-03-06	Smithkline Beecham Corporation	Nowe związki
US20070066632A1 (en) *	2005-03-25	2007-03-22	Scios, Inc.	Fused bicyclic inhibitors of TGFbeta
BRPI0609650A2 (pt) *	2005-03-25	2010-04-20	Tibotec Pharm Ltd	inibidores heterobicìlicos de hvc
EP1979348B1 (fr) *	2005-12-21	2012-01-18	Abbott Laboratories	Composes antiviraux

2009
- 2009-06-29 EP EP09774230A patent/EP2291376A2/fr not_active Withdrawn
- 2009-06-29 CA CA2727103A patent/CA2727103A1/fr not_active Abandoned
- 2009-06-29 JP JP2011516760A patent/JP2011526912A/ja active Pending
- 2009-06-29 AU AU2009267161A patent/AU2009267161B2/en not_active Ceased
- 2009-06-29 BR BRPI0914936A patent/BRPI0914936A2/pt not_active IP Right Cessation
- 2009-06-29 EA EA201100126A patent/EA201100126A1/ru unknown
- 2009-06-29 US US12/997,312 patent/US20110269758A1/en not_active Abandoned
- 2009-06-29 WO PCT/US2009/049035 patent/WO2010002779A2/fr not_active Ceased
- 2009-06-29 KR KR1020117002178A patent/KR20110025856A/ko not_active Ceased
- 2009-06-29 CN CN200980125942.XA patent/CN102083831B/zh not_active Expired - Fee Related
- 2009-06-29 MX MX2010013842A patent/MX2010013842A/es not_active Application Discontinuation
2010
- 2010-12-09 ZA ZA2010/08878A patent/ZA201008878B/en unknown
- 2010-12-30 IL IL210377A patent/IL210377A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
IL210377A (en)	2015-03-31
IL210377A0 (en)	2011-03-31
AU2009267161B2 (en)	2014-11-06
KR20110025856A (ko)	2011-03-11
ZA201008878B (en)	2012-02-29
MX2010013842A (es)	2011-01-14
EP2291376A2 (fr)	2011-03-09
BRPI0914936A2 (pt)	2015-10-20
CN102083831A (zh)	2011-06-01
EA201100126A1 (ru)	2011-08-30
AU2009267161A1 (en)	2010-01-07
HK1156611A1 (en)	2012-06-15
WO2010002779A3 (fr)	2011-03-03
JP2011526912A (ja)	2011-10-20
WO2010002779A2 (fr)	2010-01-07
US20110269758A1 (en)	2011-11-03
CN102083831B (zh)	2014-09-03

Legal Events

Date	Code	Title	Description
2014-02-07	EEER	Examination request	Effective date: 20140122
2016-08-10	FZDE	Discontinued	Effective date: 20160629

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